Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed primary supratentorial glioma.

• - WHO histologic grade 3 or 4.

• - Patients who have undergone prior treatment for low-grade glioma that has transformed to glioblastoma (biopsy proven) allowed.

• - Amenable to standard temozolomide treatment.

• - First or second recurrent disease after prior surgery and/or radiotherapy OR newly diagnosed disease that is not amenable to radiotherapy (e.g., multifocal disease) PATIENT CHARACTERISTICS: - ECOG or WHO performance status 0-2.

• - Hemoglobin ≥ 10.0 g/dL.

• - Neutrophil count ≥ 1,500/mm^3.

• - Platelet count ≥ 100,000/mm^3.

• - Bilirubin ≤ 1.5 x upper limit of normal (ULN) - Alkaline phosphatase and transaminases ≤ 2.5 x ULN.

• - Serum creatinine < 1.7 mg/dL.

• - Not pregnant or lactating.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - Clinically normal cardiac function.

• - No ischemic heart disease within the past 6 months.

• - No clinically significant abnormalities or uncontrolled cardiac arrhythmia by ECG.

• - QTc interval ≤ 450 msec (males) or ≤ 470 msec (females) by baseline 12-lead ECG.

• - No history of congenital long QTc syndrome.

• - No history of stroke.

• - No other prior or concurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal or squamous cell skin carcinoma.

• - No unstable systemic diseases.

• - No active uncontrolled infections.

• - No uncontrolled hypertension.

• - No psychological, familial, sociological, or geographical condition that would preclude study participation.

• - Must be able to swallow tablets.

PRIOR CONCURRENT THERAPY:

• - See Disease Characteristics.

• - No more than 1 prior chemotherapy regimen in the adjuvant setting or for first recurrence.

• - Prior temozolomide allowed provided there was no disease progression during temozolomide treatment or within 6 weeks of completing temozolomide treatment.

• - Prior surgery for primary brain tumor within the past 3 months allowed.

• - Patients who are receiving corticosteroid treatment must be on a stable or decreasing dose for at least 1 week before study entry.

• - At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) - At least 14 days since prior and no concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following: - Phenytoin.

• - Carbamazepine.

• - Phenobarbital.

• - More than 30 days since prior and no other concurrent investigational treatments.

• - No concurrent anticoagulant treatment (e.g., warfarin) - Low molecular weight heparin for patients who require anticoagulant therapy after starting study treatment may be allowed.

• - No concurrent routine use of colony-stimulating factors.

- No other concurrent anticancer agents

OBJECTIVES:

• - To assess if full doses of enzastaurin hydrochloride and temozolomide can be used in combination for the treatment of patients with primary gliomas.

• - To determine the recommended phase II dose.

OUTLINE: This is a multicenter study. Patients receive oral enzastaurin hydrochloride once or twice daily on days 1-28* and oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: *During the first course only, patients also receive enzastaurin hydrochloride on day -1. Patients undergo blood sample collection on day 22 of course 1 and on day 5 of course 2 for pharmacokinetic studies of enzastaurin hydrochloride. After completion of study treatment, patients are followed within 30 days and then every 3 months thereafter.